title: Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.
abstract: Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant adenovirus-based vectors have been identified as potent vaccine candidates, with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the US Food and Drug Administration (FDA) and phase I clinical trials have been initiated for two small-molecule therapeutics: anti-sense phosphorodiamidate morpholino oligomers (PMOs: AVI-6002, AVI-6003) and lipid nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy, which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms are also discussed.
authors.affiliation: Division of Pharmaceutics, The University of Texas at Austin, College of Pharmacy, PHR 4.214D, 2409 W. University Ave., 1 University Station #A1920, Austin, TX, 78712-1074, USA.
authors.forename: Jin Huk
authors.initials: JH
authors.lastname: Choi
authors.forename: Maria A
authors.initials: MA
authors.lastname: Croyle
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015195:Drug Design; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000276:immunology; D029043:Ebolavirus / Q000276:immunology / Q000302:isolation & purification*; D005822:Genetic Vectors; D019142:Hemorrhagic Fever, Ebola / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D055118:Medication Adherence; D058990:Molecular Targeted Therapy; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D056990:Post-Exposure Prophylaxis / Q000379:methods; D034741:RNA, Small Interfering / Q000008:administration & dosage
chemical_list: D046129:Ebola Vaccines; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering